Benzamycin Gel - Clinical Pharmacology

The exact mechanism by which erythromycin reduces lesions of acne vulgaris is not fully known; however, the effect appears to be due in part to the antibacterial activity of the drug.

Benzoyl peroxide has a keratolytic and desquamative effect which may also contribute to its efficacy. Benzoyl peroxide has been shown to be absorbed by the skin where it is converted to benzoic acid.

MICROBIOLOGY

Erythromycin acts by inhibition of protein synthesis in susceptible organisms by reversibly binding to 50 S ribosomal subunits, thereby inhibiting translocation of aminoacyl transfer-RNA and inhibiting polypeptide synthesis. Antagonism has been demonstrated in vitro between erythromycin, lincomycin, chloramphenicol and clindamycin.

Benzoyl peroxide is an antibacterial agent which has been shown to be effective against Propionibacterium acnes, an anaerobe found in sebaceous follicles and comedones. The antibacterial action of benzoyl peroxide is believed to be due to the release of active oxygen.

Indications and Usage for Benzamycin Gel

BENZAMYCIN Topical Gel is indicated for the topical treatment of acne vulgaris.

Contraindications

BENZAMYCIN Topical Gel is contraindicated in those individuals who have shown hypersensitivity to any of its components.

Warnings

Pseudomembranous colitis has been reported with nearly all antibacterial agents, including erythromycin, and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.

Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is one primary cause of "antibiotic-associated colitis."

After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation and treatment with an antibacterial drug clinically effective against C. difficile colitis.

Precautions

General

For topical use only; not for ophthalmic use. Concomitant topical acne therapy should be used with caution because a possible cumulative irritancy effect may occur, especially with the use of peeling, desquamating or abrasive agents. If severe irritation develops, discontinue use and institute appropriate therapy.

The use of antibiotic agents may be associated with the overgrowth of nonsusceptible organisms including fungi. If this occurs, discontinue use and take appropriate measures.

Avoid contact with eyes and all mucous membranes.

Information for Patients

Patients using BENZAMYCIN Topical Gel should receive the following information and instructions:

1.

This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes, nose, mouth, and all mucous membranes.

2.

This medication should not be used for any disorder other than that for which it was prescribed.

3.

Patients should not use any other topical acne preparation unless otherwise directed by physician.

4.

Patients should report to their physician any signs of local adverse reactions.

5.

BENZAMYCIN Topical Gel may bleach hair or colored fabric.

6.

Keep product refrigerated and discard after 3 months.

CARCINOGENESIS, MUTAGENESIS AND IMPAIRMENT OF FERTILITY

Data from a study using mice known to be highly susceptible to cancer suggests that benzoyl peroxide acts as a tumor promoter. The clinical significance of this is unknown.

No animal studies have been performed to evaluate the carcinogenic and mutagenic potential or effects on fertility of topical erythromycin. However, long-term (2-year) oral studies in rats with erythromycin ethylsuccinate and erythromycin base did not provide evidence of tumorigenicity. There was no apparent effect on male or female fertility in rats fed erythromycin (base) at levels up to 0.25% of diet.

Pregnancy

Teratogenic Effects

Animal reproduction studies have not been conducted with BENZAMYCIN Topical Gel or benzoyl peroxide.

There was no evidence of teratogenicity or any other adverse effect on reproduction in female rats fed erythromycin base (up to 0.25% diet) prior to and during mating, during gestation and through weaning of two successive litters.

There are no well-controlled trials in pregnant women with BENZAMYCIN Topical Gel. It also is not known whether BENZAMYCIN Topical Gel can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. BENZAMYCIN Topical Gel should be given to a pregnant woman only if clearly needed.

Nursing Women

It is not known whether BENZAMYCIN Topical Gel is excreted in human milk after topical application. However, erythromycin is excreted in human milk following oral and parenteral erythromycin administration. Therefore, caution should be exercised when erythromycin is administered to a nursing woman.

Pediatric Use

Safety and effectiveness of this product in pediatric patients below the age of 12 have not been established.

Adverse Reactions

In controlled clinical trials, the incidence of adverse reactions associated with the use of BENZAMYCIN Topical Gel was approximately 3%. These were dryness and urticarial reaction.

The following additional local adverse reactions have been reported occasionally: irritation of the skin including peeling, itching, burning sensation, erythema, inflammation of the face, eyes and nose, and irritation of the eyes. Skin discoloration, oiliness and tenderness of the skin have also been reported.

To report SUSPECTED ADVERSE REACTIONS, contact Valeant Pharmaceuticals North America LLC, at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Benzamycin Gel Dosage and Administration

BENZAMYCIN Topical Gel should be applied twice daily, morning and evening, or as directed by a physician, to affected areas after the skin is thoroughly washed, rinsed with warm water and gently patted dry.

How Supplied and Compounding Directions

Size

Benzoyl

Active Erythromycin

70% Ethyl Alcohol

(Net Weight)

NDC 0187-

Peroxide Gel

Powder

(In Plastic Vial)

To Be Added

46.6 grams

5205-46

40 grams

1.6 grams

6 mL

(as dispensed)

Prior to dispensing, tap vial until all powder flows freely. Add indicated amount of room temperature 70% ethyl alcohol to vial (to the mark) and immediately shake to completely dissolve erythromycin. Add this solution to gel and stir until homogeneous in appearance (1 to 1½ minutes). BENZAMYCIN Topical Gel should then be stored under refrigeration. Do not freeze. Place a 3-month expiration date on the label.

NOTE: Prior to reconstitution, store at room temperature between 15°C to 30°C (59°F to 86°F).

After reconstitution, store under refrigeration between 2°C to 8°C (36°F to 46°F).